# Innovative Cell Therapy for Pediatric Acute Myeloid Leukemia

> **NIH NIH R21** · STANFORD UNIVERSITY · 2021 · $93,389

## Abstract

Abstract
The parent R21 proposal 1R21CA245468-01A1 "Innovative Cell Therapy for Pediatric Acute Myeloid Leukemia"
is designed to address the mechanism of pediatric acute myeloid leukemia (pAML) blast resistance to LV-10
cell-mediated killing. LV-10 cells are engineered type 1 regulatory T cells (Tr1) that represent a promising therapy
for pAML because of their inherent anti-myeloid tumor cytotoxicity, but in pilot experiments, a subset of primary
pAML blasts resisted LV-10 cell killing. RNA-seq revealed two candidate genes that could contribute to pAML
resistance to killing. These genes could also be used as biomarkers of resistant pAML, which is important for
downstream clinical translation of LV-10 cells. However, a larger RNA-seq dataset is required for sufficiently
powered biomarker discovery. Aim 1 of the parent proposal will assess the sensitivity of 45 new pAML blasts to
LV-10 mediated killing, which in addition to the pilot samples, provides sufficient power for biomarker discovery.
Aim 1 of the supplemental proposal will perform bulk RNAseq analyses on these 45 pAML blasts to identify
potential new biomarkers of resistance. Further, the LV-10 cells are currently expanded using a mixture of healthy
human donor-derived peripheral blood mononuclear cells (PBMC) as feeder cells, which introduces donor-to-
donor variability to LV-10 expansion, phenotype and function. Before the clinical translation of LV-10 cells, it is
essential to identify an alternative artificial expansion system that provides a functionally uniform and GMP com-
pliant cell product. These systems are already in place for other T cell-based therapies. In aim 2 of the supple-
mental proposal, we will compare the effect of 2 artificial antigen-presenting cell (aAPC) systems, TransAct and
ImmunoCult, to the traditional PBMC feeders, on LV-10 cell expansion, phenotype, cytokine production, degran-
ulation and AML killing. Altogether, this data will reveal: 1) additional genes that play a role in pAML resistance
to LV-10 killing, which can be used in the future to reverse this resistance or screen pAML patients eligible for
LV-10 cell therapy; and 2) optimal aAPC system for LV-10 cell expansion. As such, this supplemental proposal
will complement the aims of the parent proposal, and it's focus on pAML transcriptome analysis and a novel cell
therapy for pAML. Furthermore , execution of the experiments required to achieve these goals will provide the
Candidate with essential background and skills in cancer immunology and immunotherapy, paving the way to
his enrollment into graduate school and a career path as a cancer immunologist.

## Key facts

- **NIH application ID:** 10283948
- **Project number:** 3R21CA245468-01A1S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Maria Grazia Roncarolo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $93,389
- **Award type:** 3
- **Project period:** 2021-03-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283948

## Citation

> US National Institutes of Health, RePORTER application 10283948, Innovative Cell Therapy for Pediatric Acute Myeloid Leukemia (3R21CA245468-01A1S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10283948. Licensed CC0.

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